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Article ; Online: Avian influenza

Peeters, B.P.H.

Tijdschrift voor Diergeneeskunde

Use of recombinant DNA techniques in research and vaccine development

2008 Volume 133, Issue 22

Abstract: Informatie omtrent de stand van zaken betreffende het ... ...

Abstract	Informatie omtrent de stand van zaken betreffende het influenzavirusonderzoek
Keywords	avian influenza viruses ; genetic engineering ; recombinant dna ; research ; aviaire influenzavirussen ; genetische modificatie ; onderzoek
Language	English
Publishing country	nl
Document type	Article ; Online
ZDB-ID	422558-2
ISSN	0040-7453
ISSN	0040-7453
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Article ; Online: Field vaccinated chickens with low antibody titres show equally insufficient protection against matching and non-matching genotypes of virulent Newcastle disease virus.

Dortmans, J C F M / Venema-Kemper, S / Peeters, B P H / Koch, G

Veterinary microbiology

2014 Volume 172, Issue 1-2, Page(s) 100–107

Abstract: Newcastle disease (ND) is a severe threat to the poultry industry and is caused by virulent strains of Newcastle disease virus (NDV). Many countries maintain a vaccination policy, but NDV is rapidly evolving as shown by the discovery of several new ... ...

Abstract	Newcastle disease (ND) is a severe threat to the poultry industry and is caused by virulent strains of Newcastle disease virus (NDV). Many countries maintain a vaccination policy, but NDV is rapidly evolving as shown by the discovery of several new genotypes in the last decades. We tested the efficacy of the currently used classical commercial ND vaccine based on the genotype II strain VG/GA, applied under standard field conditions, against outbreak strains. Field vaccinated broilers were challenged with four different viruses belonging to genotype II, V or VII. A large proportion of field vaccinated broilers showed suboptimal immunity and the protection level against early and recent NDV isolates was dramatically low. Furthermore, there were no significant differences in protection afforded by a genotype II vaccine against a genotype II virus challenge compared to a challenge with viruses belonging to the other genotypes. This study suggests that the susceptibility of vaccinated poultry to NDV infection is not the result of vaccine mismatch, but rather of poor vaccination practices.
MeSH term(s)	Animals ; Antibodies, Viral/blood ; Chickens/virology ; Disease Susceptibility ; Genotype ; Immunity, Active ; Newcastle Disease/immunology ; Newcastle Disease/mortality ; Newcastle Disease/prevention & control ; Newcastle Disease/virology ; Newcastle disease virus/classification ; Newcastle disease virus/genetics ; Newcastle disease virus/immunology ; Phylogeny ; Survival Analysis ; Vaccination/veterinary ; Viral Vaccines/administration & dosage ; Viral Vaccines/immunology
Chemical Substances	Antibodies, Viral ; Viral Vaccines
Language	English
Publishing date	2014-08-06
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	753154-0
ISSN	1873-2542 ; 0378-1135
ISSN (online)	1873-2542
ISSN	0378-1135
DOI	10.1016/j.vetmic.2014.05.004
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Book ; Online: Role of Vaccination-Induced Immunity and Antigenic Distance in Transmission Dynamics Investigated Using Highly Pathogenic Avian influenza (HPAI) H5N1 Virus Escape Mutants

Sitaras, I. / Peeters, B.P.H. / de Jong, M.C.M.

2015

Abstract: Background:Evolution of avian influenza viruses – especially of the highly pathogenic avian influenza (HPAI) H5N1 subtype – is a major issue, since HPAI H5N1 epidemics are associated with huge economic losses and connected to human morbidity and ... ...

Abstract	Background:Evolution of avian influenza viruses – especially of the highly pathogenic avian influenza (HPAI) H5N1 subtype – is a major issue, since HPAI H5N1 epidemics are associated with huge economic losses and connected to human morbidity and mortality. Vaccination as a means to prevent transmission has oftentimes been reported as being ineffective and as a potential driving force in the selection of immune escape mutants. It is therefore essential to study how mutations are selected due to immune pressure, as well as, what is the effect on transmission given the antigenic distance between vaccine and challenge strains after selection has taken place. Methods:We have selected for escape mutants of HPAI H5N1 A/turkey/Turkey/1/2005 by repeated in vitro exposure to homologous polyclonal sera. We characterised the mutants genetically and antigenically. We conducted two sets of transmission experiments to evaluate the transmission dynamics of the parent strains in animals vaccinated with high and low doses of our selected immune escape mutants. Finally, we employed mathematical models to examine the effect that antigenic distance between vaccine and challenge strains has on the vaccination-induced antibody level and therewith on virus transmission. Results: After 42 rounds of selection we identified 5 amino acid mutations, most of which located in areas of antigenic importance, also known to be prone to variation due to immune pressure. We show that genetic and antigenic distance increases with passage number. Our transmission experiments and mathematical analyses demonstrate that antigenic distance between vaccine and challenge strains is not a major factor in the transmission dynamics of the strains used in this study, as the effect of antibody levels against the challenge viruses is much larger than the small effect of antigenic distance. The reduction in transmission between animals with high antibody titres is mainly caused by lower infectivity and not by a change in susceptibility. Conclusions:Although ...
Keywords	Life Science
Subject code	570
Language	English
Publishing country	nl
Document type	Book ; Online
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Article ; Online: Intranasal adminstration of a live-attenuated recombinant newcastle disease virus expressing the SARS-CoV-2 Spike protein induces high neutralizing antibody levels and protects from experimental challenge infection in hamsters

de Swart, R.L. / de Leeuw, O.S. / Oreshkova, N.D. / Gerhards, N.M. / Albulescu, Irina C. / Vreman, S. / Gonzales Rojas, J.L. / Maas, H.A. / Van Kuppeveld, Frank J.M. / Soema, Peter / Bosch, Berend Jan / Peeters, B.P.H.

Vaccine

2022 Volume 40, Issue 33

Abstract: The emergence of SARS-CoV-2 in December 2019 resulted in the COVID-19 pandemic. Recurring disease outbreaks repeatedly overloaded the public health sector and severely affected the global economy. We developed a candidate COVID-19 vaccine based on a ... ...

Abstract	The emergence of SARS-CoV-2 in December 2019 resulted in the COVID-19 pandemic. Recurring disease outbreaks repeatedly overloaded the public health sector and severely affected the global economy. We developed a candidate COVID-19 vaccine based on a recombinant Newcastle disease virus (NDV) vaccine vector, encoding a pre-fusion stabilized full-length Spike protein obtained from the original SARS-CoV-2 Wuhan isolate. Vaccination of hamsters by intra-muscular injection or intra-nasal instillation induced high neutralizing antibody responses. Intranasal challenge infection with SARS-CoV-2 strain Lelystad demonstrated that both vaccination routes provided partial protection in the upper respiratory tract, and almost complete protection in the lower respiratory tract, as measured by suppressed viral loads and absence of histological lung lesions. Activity wheel measurements demonstrated that animals vaccinated by intranasal inoculation rapidly recovered to normal activity. NDV constructs encoding the spike of SARS-CoV-2 may be attractive candidates for development of intra-nasal COVID-19 booster vaccines
Keywords	Life Science
Subject code	570
Language	English
Publishing country	nl
Document type	Article ; Online
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
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Article ; Online: Mutation of the second sialic acid-binding of influenza A virus neuraminidase drives compensatory mutations in hemagglutinin

Du, Wenjuan / Wolfert, Margreet A. / Peeters, B.P.H. / van Kuppeveld, Frank J.M. / Boons, Geert-Jan / de Vries, Erik / de Haan, Cornelis A.M.

PLoS Pathogens

2020 Volume 16, Issue 8

Abstract: Influenza A viruses (IAVs) cause seasonal epidemics and occasional pandemics. Most pandemics occurred upon adaptation of avian IAVs to humans. This adaptation includes a hallmark receptor-binding specificity switch of hemagglutinin (HA) from avian-type ... ...

Abstract	Influenza A viruses (IAVs) cause seasonal epidemics and occasional pandemics. Most pandemics occurred upon adaptation of avian IAVs to humans. This adaptation includes a hallmark receptor-binding specificity switch of hemagglutinin (HA) from avian-type α2,3- to human-type α2,6-linked sialic acids. Complementary changes of the receptor-destroying neuraminidase (NA) are considered to restore the precarious, but poorly described, HA-NA-receptor balance required for virus fitness. In comparison to the detailed functional description of adaptive mutations in HA, little is known about the functional consequences of mutations in NA in relation to their effect on the HA-NA balance and host tropism. An understudied feature of NA is the presence of a second sialic acid-binding site (2SBS) in avian IAVs and absence of a 2SBS in human IAVs, which affects NA catalytic activity. Here we demonstrate that mutation of the 2SBS of avian IAV H5N1 disturbs the HA-NA balance. Passaging of a 2SBS-negative H5N1 virus on MDCK cells selected for progeny with a restored HA-NA balance. These viruses obtained mutations in NA that restored a functional 2SBS and/or in HA that reduced binding of avian-type receptors. Importantly, a particular HA mutation also resulted in increased binding of human-type receptors. Phylogenetic analyses of avian IAVs show that also in the field, mutations in the 2SBS precede mutations in HA that reduce binding of avian-type receptors and increase binding of human-type receptors. Thus, 2SBS mutations in NA can drive acquisition of mutations in HA that not only restore the HA-NA balance, but may also confer increased zoonotic potential.
Keywords	Life Science
Subject code	616
Language	English
Publishing country	nl
Document type	Article ; Online
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7366
ISSN (online)	1553-7374
ISSN	1553-7366
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Article ; Online: A comparative infection study of pigeon and avian paramyxovirus type 1 viruses in pigeons: evaluation of clinical signs, virus shedding and seroconversion.

Dortmans, J C F M / Koch, G / Rottier, P J M / Peeters, B P H

Avian pathology : journal of the W.V.P.A

2011 Volume 40, Issue 2, Page(s) 125–130

Abstract: The pathogenesis of pigeon paramyxovirus type 1 (PPMV-1) isolate AV324/96 and of its recombinant derivative, rgAV324, was studied in pigeons. For comparison, the virulent chicken virus FL-Herts, which is a recombinant derivative of strain Herts/33, was ... ...

Abstract	The pathogenesis of pigeon paramyxovirus type 1 (PPMV-1) isolate AV324/96 and of its recombinant derivative, rgAV324, was studied in pigeons. For comparison, the virulent chicken virus FL-Herts, which is a recombinant derivative of strain Herts/33, was also included. After inoculation by the combined intraocular, intranasal and intratracheal route, clinical signs, virus shedding and serological responses were examined. Clinical signs were observed only in the FL-Herts-infected group. All virus-inoculated pigeons had positive tracheal swabs until 5 days post infection. However, only the AV324/96-infected and rgAV324-infected birds, and not the FL-Herts-infected birds, shed virus in the cloaca. The AV324/96-infected pigeons showed higher mean antibody titres than the rgAV324-infected birds, whereas the antibody titres of the FL-Herts-infected group were rather low. The results show that the pigeon strain AV324 is not virulent for pigeons, but underlines the potential risk of poultry becoming infected by PPMV-1 shed by non-symptomatic pigeons.
MeSH term(s)	Animals ; Antibodies, Viral/biosynthesis ; Antibodies, Viral/blood ; Chickens/virology ; Cloaca/virology ; Columbidae/virology ; Newcastle Disease/immunology ; Newcastle Disease/pathology ; Newcastle Disease/virology ; Newcastle disease virus/isolation & purification ; Newcastle disease virus/pathogenicity ; Newcastle disease virus/physiology ; Poultry/virology ; Poultry Diseases/immunology ; Poultry Diseases/pathology ; Poultry Diseases/virology ; Trachea/virology ; Virulence ; Virus Shedding/physiology
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2011-04
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1476380-1
ISSN	1465-3338 ; 0307-9457
ISSN (online)	1465-3338
ISSN	0307-9457
DOI	10.1080/03079457.2010.542131
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Article ; Online: Passaging of a Newcastle disease virus pigeon variant in chickens results in selection of viruses with mutations in the polymerase complex enhancing virus replication and virulence.

Dortmans, J C F M / Rottier, P J M / Koch, G / Peeters, B P H

The Journal of general virology

2011 Volume 92, Issue Pt 2, Page(s) 336–345

Abstract: Some Newcastle disease virus (NDV) variants isolated from pigeons (pigeon paramyxovirus type 1; PPMV-1) do not show their full virulence potential for domestic chickens but may become virulent upon spread in these animals. In this study we examined the ... ...

Abstract	Some Newcastle disease virus (NDV) variants isolated from pigeons (pigeon paramyxovirus type 1; PPMV-1) do not show their full virulence potential for domestic chickens but may become virulent upon spread in these animals. In this study we examined the molecular changes responsible for this gain of virulence by passaging a low-pathogenic PPMV-1 isolate in chickens. Complete genome sequencing of virus obtained after 1, 3 and 5 passages showed the increase in virulence was not accompanied by changes in the fusion protein--a well known virulence determinant of NDV--but by mutations in the L and P replication proteins. The effect of these mutations on virulence was confirmed by means of reverse genetics using an infectious cDNA clone. Acquisition of three amino acid mutations, two in the L protein and one in the P protein, significantly increased virulence as determined by intracerebral pathogenicity index tests in day-old chickens. The mutations enhanced virus replication in vitro and in vivo and increased the plaque size in infected cell culture monolayers. Furthermore, they increased the activity of the viral replication complex as determined by an in vitro minigenome replication assay. Our data demonstrate that PPMV-1 replication in chickens results in mutations in the polymerase complex rather than the viral fusion protein, and that the virulence level of pigeon paramyxoviruses is directly related to the activity of the viral replication complex.
MeSH term(s)	Animals ; Base Sequence ; Chickens ; Columbidae ; DNA-Directed RNA Polymerases/genetics ; DNA-Directed RNA Polymerases/metabolism ; Gene Expression Regulation, Viral ; Genome, Viral ; Mutation ; Newcastle Disease/virology ; Newcastle disease virus/classification ; Newcastle disease virus/genetics ; Newcastle disease virus/pathogenicity ; Newcastle disease virus/physiology ; Quail ; Selection, Genetic ; Serial Passage/veterinary ; Specific Pathogen-Free Organisms ; Viral Proteins/genetics ; Virulence ; Virus Replication
Chemical Substances	Viral Proteins ; DNA-Directed RNA Polymerases (EC 2.7.7.6)
Language	English
Publishing date	2011-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	219316-4
ISSN	1465-2099 ; 0022-1317
ISSN (online)	1465-2099
ISSN	0022-1317
DOI	10.1099/vir.0.026344-0
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Article ; Online: Newcastle disease virus outbreaks

Dortmans, J.C.F.M. / Peeters, B.P.H. / Koch, G.

Veterinary Microbiology

Vaccine mismatch or inadequate appication?

2012 Volume 160, Issue 1-2

Abstract: Newcastle disease (ND) is one of the most important diseases of poultry, and may cause devastating losses in the poultry industry worldwide. Its causative agent is Newcastle disease virus (NDV), also known as avian paramyxovirus type 1. Many countries ... ...

Abstract	Newcastle disease (ND) is one of the most important diseases of poultry, and may cause devastating losses in the poultry industry worldwide. Its causative agent is Newcastle disease virus (NDV), also known as avian paramyxovirus type 1. Many countries maintain a stringent vaccination policy against ND, but there are indications that ND outbreaks can still occur despite intensive vaccination. It has been argued that this may be due to antigenic divergence between the vaccine strains and circulating field strains. Here we present the complete genome sequence of a highly virulent genotype VII virus (NL/93) obtained from vaccinated poultry during an outbreak of ND in the Netherlands in 1992–1993. Using this strain, we investigated whether the identified genetic evolution of NDV is accompanied by antigenic evolution. In this study we show that a live vaccine that is antigenically adapted to match the genotype VII NL/93 outbreak strain does not provide increased protection compared to a classic genotype II live vaccine. When challenged with the NL/93 strain, chickens vaccinated with a classic vaccine were completely protected against clinical disease and mortality and virus shedding was significantly reduced, even with a supposedly suboptimal vaccine dose. These results suggest that it is not antigenic variation but rather poor flock immunity due to inadequate vaccination practices that may be responsible for outbreaks and spreading of virulent NDV field strains.
Keywords	chickens ; china ; fusion protein ; genotype vii ; molecular epidemiology ; paramyxovirus type-1 ; phylogenetic-relationships ; shedding following vaccination ; strains ; western-europe
Subject code	570
Language	English
Publishing country	nl
Document type	Article ; Online
ZDB-ID	753154-0
ISSN	1873-2542 ; 0378-1135
ISSN (online)	1873-2542
ISSN	0378-1135
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The viral replication complex is associated with the virulence of Newcastle disease virus.

Dortmans, J C F M / Rottier, P J M / Koch, G / Peeters, B P H

Journal of virology

2010 Volume 84, Issue 19, Page(s) 10113–10120

Abstract: Virulent strains of Newcastle disease virus ([NDV] also known as avian paramyxovirus type 1) can be discriminated from low-virulence strains by the presence of multiple basic amino acid residues at the proteolytic cleavage site of the fusion (F) protein. ...

Abstract	Virulent strains of Newcastle disease virus ([NDV] also known as avian paramyxovirus type 1) can be discriminated from low-virulence strains by the presence of multiple basic amino acid residues at the proteolytic cleavage site of the fusion (F) protein. However, some NDV variants isolated from pigeons (pigeon paramyxovirus type 1 [PPMV-1]) have low levels of virulence, despite the fact that their F protein cleavage sites contain a multibasic amino acid sequence and have the same functionality as that of virulent strains. To determine the molecular basis of this discrepancy, we examined the role of the internal proteins in NDV virulence. Using reverse genetics, the genes encoding the nucleoprotein (NP), phosphoprotein (P), matrix protein (M), and large polymerase protein (L) were exchanged between the nonvirulent PPMV-1 strain AV324 and the highly virulent NDV strain Herts. Recombinant viruses were evaluated for their pathogenicities and replication levels in day-old chickens, and viral genome replication and plaque sizes were examined in cell culture monolayers. We also tested the contributions of the individual NP, P, and L proteins to the activity of the viral replication complex in an in vitro replication assay. The results showed that the replication proteins of Herts are more active than those of AV324 and that the activity of the viral replication complex is directly related to virulence. Although the M protein affected viral replication in vitro, it had only a minor effect on virulence.
MeSH term(s)	Animals ; Base Sequence ; Cell Line ; Chickens ; Columbidae ; DNA, Viral/genetics ; Genome, Viral ; In Vitro Techniques ; Newcastle Disease/virology ; Newcastle disease virus/genetics ; Newcastle disease virus/isolation & purification ; Newcastle disease virus/pathogenicity ; Newcastle disease virus/physiology ; Nucleocapsid Proteins ; Nucleoproteins/genetics ; Nucleoproteins/physiology ; Phosphoproteins/genetics ; Phosphoproteins/physiology ; Quail ; Recombination, Genetic ; Viral Matrix Proteins/genetics ; Viral Matrix Proteins/physiology ; Viral Proteins/genetics ; Viral Proteins/physiology ; Virulence/genetics ; Virulence/physiology ; Virus Replication/genetics ; Virus Replication/physiology
Chemical Substances	DNA, Viral ; L protein, paramyxoviridae ; Nucleocapsid Proteins ; Nucleoproteins ; P phosphoprotein, Newcastle disease virus ; Phosphoproteins ; Viral Matrix Proteins ; Viral Proteins ; nucleoprotein, Newcastle disease virus
Language	English
Publishing date	2010-07-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.00097-10
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Article ; Online: Immune escape mutants of highly pathogenic avian influenza H5N1 selected using polyclonal sera

Sitaras, I. / Kalthof, D. / Beer, M. / Peeters, B.P.H. / de Jong, M.C.M.

PLoS ONE

Identification of key amino acids in the HA protein

2014 Volume 9, Issue 2

Abstract: Evolution of Avian Influenza (AI) viruses – especially of the Highly Pathogenic Avian Influenza (HPAI) H5N1 subtype – is a major issue for the poultry industry. HPAI H5N1 epidemics are associated with huge economic losses and are sometimes connected to ... ...

Abstract	Evolution of Avian Influenza (AI) viruses – especially of the Highly Pathogenic Avian Influenza (HPAI) H5N1 subtype – is a major issue for the poultry industry. HPAI H5N1 epidemics are associated with huge economic losses and are sometimes connected to human morbidity and mortality. Vaccination (either as a preventive measure or as a means to control outbreaks) is an approach that splits the scientific community, due to the risk of it being a potential driving force in HPAI evolution through the selection of mutants able to escape vaccination-induced immunity. It is therefore essential to study how mutations are selected due to immune pressure. To this effect, we performed an in vitro selection of mutants from HPAI A/turkey/Turkey/1/05 (H5N1), using immune pressure from homologous polyclonal sera. After 42 rounds of selection, we identified 5 amino acid substitutions in the Haemagglutinin (HA) protein, most of which were located in areas of antigenic importance and suspected to be prone to selection pressure. We report that most of the mutations took place early in the selection process. Finally, our antigenic cartography studies showed that the antigenic distance between the selected isolates and their parent strain increased with passage number.
Keywords	a viruses ; antigenic drift ; egypt ; evolution ; molecule ; monoclonal-antibodies ; neutralization ; poultry ; vaccination ; virus hemagglutinin
Subject code	570
Language	English
Publishing country	nl
Document type	Article ; Online
ZDB-ID	2267670-3
ISSN	1932-6203
ISSN	1932-6203
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